Hepatitis C virus replication in mice with chimeric human livers
Hepatitis C virus replication in mice with chimeric human livers
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DOI：
10.1038/90968
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发表时间：
2001-08-01
期刊：
影响因子：
82.9
通讯作者：
Kneteman, NM
中科院分区：
文献类型：
--
作者：
Mercer, DF;Schiller, DE;Kneteman, NM
人类丙型肝炎病毒（HCV）小动物模型的缺乏阻碍了针对这种流行病感染的抗病毒疗法的发展。通过将正常人肝细胞移植到携带纤溶酶原激活物转基因（Alb-uPA）的SCID小鼠体内，我们获得了嵌合人肝小鼠。Alb-uPA的纯合性与人类肝细胞植入水平显著升高相关，这些小鼠在接种受感染的人血清后出现高病毒滴度的HCV感染。总病毒载量最初增加了1950倍，移植肝脏中检测到负链病毒RNA证实了复制。HCV病毒蛋白定位于人肝细胞结节，并通过三代小鼠连续传代感染，证实感染性病毒颗粒的合成和释放。这些嵌合小鼠是第一个适合在体内研究人类丙型肝炎病毒的小鼠模型。
Lack of a small animal model of the human hepatitis C virus (HCV) has impeded development of antiviral therapies against this epidemic infection. By transplanting normal human hepatocytes into SCID mice carrying a plasminogen activator transgene (Alb-uPA), we generated mice with chimeric human livers. Homozygosity of Alb-uPA was associated with significantly higher levels of human hepatocyte engraftment, and these mice developed prolonged HCV infections with high viral titers after inoculation with infected human serum. Initial increases in total viral load were up to 1950-fold, with replication confirmed by detection of negative-strand viral RNA in transplanted livers. HCV viral proteins were localized to human hepatocyte nodules, and infection was serially passaged through three generations of mice confirming both synthesis and release of infectious viral particles. These chimeric mice represent the first murine model suitable for studying the human hepatitis C virus in vivo.